The study of oligopeptidases in schizophrenia

• Grant number: 12/08941-6
• Support type: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): January 01, 2013
• Effective date (End): August 09, 2015
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal researcher: Mirian Akemi Furuie Hayashi
• Grantee: Camila Miyagui Yonamine Asanuma
• Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 11/50740-5 - Prevention in schizophrenia and bipolar disorder from neuroscience to the community: a multiphase, multimodal and translational platform for research and intervention, AP.TEM
• Associated scholarship(s): 13/18805-5 - The study of oligopeptidases in schizophrenia, BE.EP.PD

Abstract

Schizophrenia (SCZ) is a severe chronic mental disease. The current body of evidence suggests that it is a multifactorial disease with genetic and environmental factors, leading to an altered neurodevelopment. Ndel1 (nuclear-distribution element-like 1) is an oligopeptidade that binds to Disrupted-in-Schizophrenia 1 (DISC1) gene product, which has been largely studied as a SCZ vulnerability marker. Interestingly, the expression of Ndel1 was found reduced in hippocampus of schizophrenic patients. POP (prolyloligopeptidase) was also found decreased in plasma of schizophrenic patients, and it has also been considered as a potential drug target for the treatment of several mental diseases, including depression and SCZ. The ACE (angiotensin I-converting enzyme) was also related to SCZ, because drug-free patients showed significantly lower levels of ACE in cerebrospinal fluid (CSF) than the neuroleptic-treated patients. The spontaneously hypertensive rats (SHRs) have been proposed as an animal model for the screening of drugs with therapeutic potential for treatment of disorders of cognitive processes. Thus, our primary objective is to compare the plasma Ndel1, POP, and ECA enzyme activity levels of patients with SCZ and healthy controls (HCs). These same measures will also be evaluated in SHR rats to elucidate the similarities between this animal model and human patients, aiming a better understanding of the molecular mechanisms underlying this mental dysfunction.

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

NANI, V, JOAO; DAL MAS, CAROLINE; YONAMINE, CAMILA M.; OTA, VANESSA K.; NOTO, CRISTIANO; BELANGERO, I, SINTIA; MARI, JAIR J.; BRESSAN, RODRIGO; CORDEIRO, QUIRINO; GADELHA, ARY; HAYASHI, MIRIAN A. F. A Study in First-Episode Psychosis Patients: Does Angiotensin I-Converting Enzyme Activity Associated With Genotype Predict Symptom Severity Reductions After Treatment With Atypical Antipsychotic Risperidone?. INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY, v. 23, n. 11, p. 721-730, NOV 2020. Web of Science Citations: 0.

DAL MAS, CAROLINE; NANI, JOAO V.; NOTO, CRISTIANO; YONAMINE, CAMILA M.; DA CUNHA, GRACCIELLE RODRIGUES; MANSUR, RODRIGO B.; OTA, VANESSA K.; BELANGERO, SINTIA IOLE; CORDEIRO, QUIRINO; KAPCZINSKI, FLAVIO; BRIETZKE, ELISA; BRESSAN, RODRIGO A.; GADELHA, ARY; HAYASHI, MIRIAN A. F. Ndel1 oligopeptidase activity as a potential biomarker of early stages of schizophrenia. SCHIZOPHRENIA RESEARCH, v. 208, p. 202-208, JUN 2019. Web of Science Citations: 2.

GADELHA, ARY; COLEMAN, JONATHAN; BREEN, GEROME; MAZZOTI, DIEGO ROBLES; YONAMINE, CAMILA M.; PELLEGRINO, RENATA; OTA, VANESSA KIYOMI; BELANGERO, SINTIA IOLE; GLESSNER, JOSEPH; SLEIMAN, PATRICK; HAKONARSON, HAKON; HAYASHI, MIRIAN A. F.; BRESSAN, RODRIGO A. Genome-wide investigation of schizophrenia associated plasma Ndel1 enzyme activity. SCHIZOPHRENIA RESEARCH, v. 172, n. 1-3, p. 60-67, APR 2016. Web of Science Citations: 4.

GADELHA, ARY; YONAMINE, CAMILA M.; OTA, VANESSA K.; OLIVEIRA, VITOR; SATO, JOAO RICARDO; BELANGERO, SINTIA I.; BRESSAN, RODRIGO A.; HAYASHI, MIRIAN A. F. ACE I/D genotype-related increase in ACE plasma activity is a better predictor for schizophrenia diagnosis than the genotype alone. SCHIZOPHRENIA RESEARCH, v. 164, n. 1-3, p. 109-114, MAY 2015. Web of Science Citations: 11.